The Host-Mediated Assay is a potentially valuable tool for use in detecting environmental compounds with mutagenic activity and is one of the three screening techniques recommended for adoption by the U.S. Food and Drug Administration as a routine mutagen test. This test can detect those chemical compounds that are converted to their genetically active forms by metabolic action of a mammalian host. In addition to its applicability to mutagen testing, the results of Host-Mediated Assay tests directly relate to chemical carcinogenicity, since most mutagenic agents are also carcinogenic. The effectiveness of the Host-Mediated Assay as a screening system will depend on its sensitivity, reliability and on our understanding of the metabolic processes that convert chemicals to mutagenic and carcinogenic agents. The investigations outlined in this proposal are designed to concentrate on these parameters of the Host-Mediated Assay and to use information resulting from such studies in the initiation of tests related to the mutagenic properties of certain chemical carcinogens.